Open AccessNrf2 deficiency aggravates PM2.5-induced cardiomyopathy by enhancing oxidative stress, fibrosis and inflammation via RIPK3-regulated mitochondrial disorder
Author(s) -
Changrong Ge,
Linfeng Hu,
Deshuai Lou,
Qiang Li,
Jing Feng,
Yekuan Wu,
Jun Tan,
Minxuan Xu
Publication year - 2020
Publication title -
aging
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.473
H-Index - 90
ISSN - 1945-4589
DOI - 10.18632/aging.102906
Subject(s) - oxidative stress , inflammation , fibrosis , cardiomyopathy , medicine , mitochondrion , microbiology and biotechnology , biology , heart failure
PM 2.5 is a well-known air pollutant threatening public health, and long-term exposure to PM 2.5 increases the risk of cardiovascular diseases. Nrf2 plays a pivotal role in the amelioration of PM 2.5 -induced lung injury. However, if Nrf2 is involved in PM 2.5 -induced heart injury, and the underlying molecular mechanisms have not been explored. In this study, wild type (Nrf2 +/+ ) and Nrf2 knockout (Nrf2 -/- ) mice were exposed to PM 2.5 for 6 months. After PM 2.5 exposure, Nrf2 -/- mice developed severe physiological changes, lung injury and cardiac dysfunction. In the PM 2.5 -exposed hearts, Nrf2 deficiency caused significant collagen accumulation through promoting the expression of fibrosis-associated signals. Additionally, Nrf2 -/- mice exhibited greater oxidative stress in cardiac tissues after PM 2.5 exposure. Furthermore, PM 2.5 -induced inflammation in heart samples were accelerated in Nrf2 -/- mice through promoting inhibitor of α/nuclear factor κB (IκBα/NF-κB) signaling pathways. We also found that Nrf2 -/- aggravated autophagy initiation and glucose metabolism disorder in hearts of mice with PM 2.5 challenge. Cardiac receptor-interacting protein kinase 3 (RIPK3) expression triggered by PM 2.5 was further enhanced in mice with the loss of Nrf2. Collectively, these results suggested that strategies for enhancing Nrf2 could be used to treat PM 2.5 -induced cardiovascular diseases.